MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model

  • Acta Cir Bras. 2019 Aug 19;34(6):e201900602. doi: 10.1590/s0102-865020190060000002.
Yezhou Shen  1 ,  Jiaoyang Yu  2 ,  Yunyan Jing  2 ,  Jian Zhang  3
Affiliations
  • 1. Bachelor, Intensive Care Unit, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China. Conception and design of the study, acquisition of data, technical procedures, manuscript preparation and writing.
  • 2. Master, Intensive Care Unit, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China. Technical procedures, acquisition of data.
  • 3. Bachelor, Intensive Care Unit, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China. Statistical analysis, interpretation of data.
PMID: 31432993 DOI: 10.1590/s0102-865020190060000002
Abstract

Purpose: To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI.

Methods: Serum from Sepsis and healthy patients was collected, Sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved Caspase-3 and Bcl-2, cell viability, relative Caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay.

Results: MiR-106a was up-regulated in serum of Sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased Caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of Caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells.

Conclusion: MiR-106a aggravated LPS-induced inflammation and Apoptosis of TCMK-1 cells via regulating THBS2 expression.

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